Equitable inclusion of diverse populations in oncology clinical trials: deterrents and drivers.

The burden of cancer exerts a disproportionate impact across different regions and population subsets. Disease-specific attributes, coupled with genetic and socioeconomic factors, significantly influence cancer treatment outcomes. Precision oncology promises the development of safe and effective options for specific ethnic phenotypes and clinicodemographic profiles. Currently, clinical trials are concentrated in resource-rich geographies with younger, healthier, white, educated, and empowered populations. Vulnerable and marginalized people are often deprived of opportunities to participate in clinical trials. Despite consistent endeavors by regulators, industry, and other stakeholders, factors including diversity in trial regulations and patient and provider-related cultural, logistic, and operational barriers limit the inclusiveness of clinical trials. Understanding and addressing these constraints by collaborative actions involving regulatory initiatives, industry, patient advocacy groups, community engagement in a culturally sensitive manner, and designing and promoting decentralized clinical trials are vital to establishing a clinical research ecosystem that promotes equity in the representation of population subgroups.

Novel nanostructured lipid carriers loading Apigenin for anterior segment ocular pathologies.

Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation.

Back on top: Resuspended by dredging and other environmental disturbances, organochlorine compounds may affect the health of a dolphin population in a tropical estuary, Sepetiba Bay.

Organochlorine compounds (OCs) are persistent organic pollutants linked to damaging the immune and endocrine systems, leading to a greater susceptibility to infectious diseases at high concentrations. Sepetiba Bay, in the Southeastern Brazilian coast, historically presents anthropogenic activities and environmental contamination that could negatively impact resident populations. In this context, this study aimed to investigate the temporal trends in the accumulation of organochlorine compounds over a 12-year database in the Guiana dolphins' (Sotalia guianensis) resident population from Sepetiba Bay, including individuals collected before, during, and after an unusual mortality event triggered by morbillivirus (n = 85). The influence of biological parameters was also evaluated. The OCs concentrations in the blubber ranged from 0.98 to 739 µg/g of ΣPCB; 0.08-130 µg/g of ΣDDT; <0.002-4.56 µg/g of mirex; <0.002-1.84 µg/g of ΣHCH and <0.001-0.16 µg/g of HCB in lipid weight. Increased temporal trends were found for OCs in Guiana dolphins coinciding with periods of large events of dredging in the region. In this way, our findings suggest that the constant high OCs concentrations throughout the years in this Guiana dolphin population are a result of the constant environmental disturbance in the area, such as dredging. These elevated OCs levels, e.g., ΣPCB concentrations found above the known thresholds, may impair the response of the immune system during outbreak periods, which could lead the population to a progressive decline.

Influenza A infections: predictors of disease severity.

Influenza affects approximately 10% of the world's population annually. It is associated with high morbidity and mortality rates due to its propensity to progress to severe acute respiratory infection, leading to 10-40% of hospitalized patients needing intensive care. Characterizing the multifactorial predictors of poor prognosis is essential for developing strategies against this disease. This study aimed to identify predictors of disease severity in influenza A-infected (IFA-infected) patients and to propose a prognostic score. A retrospective cross-sectional study was conducted with 142 IFA-infected out- and inpatients treated at a tertiary hospital between 2010 and 2018. The viral subtypes, hemagglutinin mutations, viral load, IL-28B SNPs, and clinical risk factors were evaluated according to the patient's ICU admission. Multivariate analysis identified the following risk factors for disease severity: neuromuscular diseases (OR = 7.02; 95% CI = 1.18-41.75; p = 0.032), cardiovascular diseases (OR = 5.47; 95% CI = 1.96-15.27; p = 0.001), subtype (H1N1) pdm09 infection (OR = 2.29; 95% CI = 1.02-5.15; p = 0.046), and viral load (OR = 1.43; 95% CI = 1.09-1.88; p = 0.009). The prognosis score for ICU admission is based on these predictors of severity presented and ROC curve AUC = 0.812 (p < 0.0001). Our results identified viral and host predictors of disease severity in IFA-infected patients, yielding a prognostic score that had a high performance in predicting the IFA patients' ICU admission and better results than a viral load value alone. However, its implementation in health services needs to be validated in a broader population.

Determinants and impact of alexithymia on quality of life in Parkinson's disease.

INTRODUCTION: Alexithymia is a neuropsychiatric symptom conceptualized as difficulty identifying and describing feelings. Although associated with other non-motor symptoms, mainly neuropsychiatric, alexithymia may present as an isolated symptom in persons with Parkinson's Disease (PwP). The objective of the study is to identify determinants of alexithymia and its association with quality of life (QoL) in Parkinson's disease. METHODS: Subjects with Parkinson's disease were recruited. The following instruments were applied: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Toronto alexithymia scale (TAS-20) and Parkinson's Disease Questionnaire (PDQ-8). Matched healthy controls were screened using TAS-20. Clinical and demographical variables were compared between alexithymic and non-alexithymic. Regression models were used to find determinants of alexithymia. Impact of alexithymia on QoL was estimated with a linear regression model. RESULTS: 98 patients were included. 56.1% PwP and 28.8% controls were alexithymic (p<0.001). Education level (OR 0.86) and NMSS urinary score (OR 1.09) determined alexithymia as well as TAS-20 score. Alexithymia was an independent determinant of QoL. CONCLUSIONS: Alexithymia is a prevalent independent non-motor symptom in PwP with impact on QoL. Low education level and urinary symptoms are important determinants of alexithymia.

Determinants and impact of alexithymia on quality of life in Parkinson’s disease / Determinantes e impacto de la alexitimia en la calidad de vida en la enfermedad de Parkinson

Introduction: Alexithymia is a neuropsychiatric symptom conceptualized as difficulty iden-tifying and describing feelings. Although associated with other non-motor symptoms, mainlyneuropsychiatric, alexithymia may present as an isolated symptom in persons with Parkinson’sDisease (PwP). The objective of the study is to identify determinants of alexithymia and itsassociation with quality of life (QoL) in Parkinson’s disease. Methods: Subjects with Parkinson’s disease were recruited. The following instruments wereapplied: Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS),Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Toronto alexithymiascale (TAS-20) and Parkinson’s Disease Questionnaire (PDQ-8). Matched healthy controls werescreened using TAS-20. Clinical and demographical variables were compared between alex-ithymic and non-alexithymic. Regression models were used to find determinants of alexithymia.Impact of alexithymia on QoL was estimated with a linear regression model.Results: 98 patients were included. 56.1% PwP and 28.8% controls were alexithymic (p < 0.001).Education level (OR 0.86) and NMSS urinary score (OR 1.09) determined alexithymia as well asTAS-20 score. Alexithymia was an independent determinant of QoL. Conclusions: Alexithymia is a prevalent independent non-motor symptom in PwP with impacton QoL. Low education level and urinary symptoms are important determinants of alexithymia.(AU)

Introducción: La alexitimia es un rasgo neuropsiquiátrico conceptualizado como la dificul-tad para identificar y describir sentimientos. Aunque está asociado con otros síntomas nomotores, principalmente neuropsiquiátricos, sigue siendo una característica independiente delas personas con enfermedad de Parkinson (PcP). El objetivo del estudio es identificar losdeterminantes de la alexitimia y su asociación con la calidad de vida en la enfermedad deParkinson. Métodos: Se reclutaron sujetos con enfermedad de Parkinson. Se aplicaron los siguientesinstrumentos: escala unificada de la enfermedad de Parkinson de la Sociedad de Trastornosdel Movimiento (MDS-UPDRS), escala de síntomas no motores (NMSS), evaluación cognitiva deMontreal (MoCA), escala de alexitimia de Toronto (TAS-20) y cuestionario de la enfermedadde Parkinson (PDQ-8). Se incluyeron controles sanos pareados, los cuales se evaluaron usandola TAS-20. Las variables clínicas y demográficas se compararon entre pacientes alexitímicos yno alexitímicos. Se utilizaron modelos de regresión para estimar los predictores de alexitimia.El impacto de este rasgo neuropsiquiátrico en la calidad de vida se estimó con un modelo deregresión lineal. Resultados: Se incluyeron 98 pacientes. El 56,1% de PcP y el 28,8% de los controles fueronalexitímicos (p < 0,001). El nivel educativo (OR 0,86) y la puntuación urinaria del NMSS (OR1,09) determinaron la alexitimia, así como la puntuación del TAS-20. La alexitimia fue undeterminante independiente de calidad de vida. Conclusiones: La alexitimia es un síntoma independiente no motor prevalente con impactoen la calidad de vida. El bajo nivel educativo y los síntomas urinarios son determinantesimportantes de esta condición. (AU)

Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Complete Chloroplast Genome Sequence of the Western Poison Oak, Toxicodendron diversilobum (Anacardiaceae), from California.

Here, we present the complete chloroplast genome sequence of Toxicodendron diversilobum, western poison oak, from Pacific Grove, California. The genome is 159,543 bp in length, contains 133 genes, and has a high level of gene synteny to other species of Toxicodendron.

Seasonal and diel modulation of DOM in a mangrove-dominated estuary.

Rivers and estuaries are the main links between continents and oceans. The Paraíba do Sul River is among the most important rivers of the southeastern Brazilian region, carrying an average of 0.08 Tg of dissolved organic matter (DOM) to the ocean but has been facing significant changes in river discharge. In this study, we aimed to provide insights into the sources and transformations of chromophoric dissolved organic matter (CDOM) and fluorescent dissolved organic matter (FDOM) sources across a salinity gradient under changing river discharge scenarios. Three spatial surveys were performed covering the entire salinity gradient of the main estuarine channel and surrounding mangrove waters under contrasting river discharge (178 to 1240 m3 s-1), and diel sampling was conducted in the mangrove tidal creek. The characterization of DOM through the parallel factor analysis (PARAFAC) model identified six components across the river-ocean gradient and mangrove creek: terrestrial origin (C1 - fulvic acid and C2 and C3 - humic-like), protein-like (C4), tryptophan-like (C5), and tyrosine-like (C6). Our results showed a shift in DOM composition and contribution along the salinity gradient, from terrestrial (C3) to autochthonous (C5 and C6) signatures. The October-17 dry campaign was characterized by a higher proportion of microbial protein-like component C4 and a lower contribution of humic-like components compared to February-17 and March-18 across the salinity gradient with an increase in the mixing zone. The DOM compositions of the February 17 dry and March 18 wet campaigns were similar. Additionally, the March-18 wet campaign, marked by the highest river discharge, showed higher inputs of terrestrial DOM (C1-C3 components) compared to February-17 in the estuary, which allowed DOM to be transported rather than transformed. The mangrove diel study showed that tidal fluctuations are also an important driver of carbon input to the mangrove creek with a possible impact on DOM composition in estuarine waters.

Predictors and Outcomes for COVID-19 Re-Admissions in the Anticipate Cohort.

Aims To describe readmissions of hospitalised patients with COVID-19, define predictors of readmission and explore the long term outcomes using the SF-12 score compared to patients who were not readmitted and those not hospitalised. Methods A single centre retrospective in North Inner-City Dublin. Recruitment was done through a COVID follow up clinic. Predictors of readmission and SF-12 scores at two timepoints post follow up at median 3 months and 12 months. Results Seventy (45%) participants were admitted, with a median age of 49.5 years (IQR 41.3-56.9), 36(51%) of whom were female. Unscheduled readmissions at ≤30 days in COVID-19 patients were 9(12.9%) and length of stay was four days (IQR 2-5). Readmissions were due to ongoing symptoms(n=9(64.3%)) or new complications(n=5(35.7%)). Mechanical ventilation and having symptoms of nausea and vomiting on index admission were predictive of readmission. (p=0.002). SF-12 scores at one year of readmitted patients were not different to patients who were never admitted at median one year follow up, p=.089. Conclusions Most readmissions were of short duration. Early follow up of patients post MV or who had nausea and vomiting on index admission should be prioritised. Wellbeing of readmitted patients was not different to those never hospitalised, at one year.

Complete Genome Sequence of Paraclostridium bifermentans DSM 14991.

The complete genome sequence of Paraclostridium bifermentans was obtained by assembly of Illumina and Oxford Nanopore (ONT) reads. The sequence will enable study into the organism's ability to biohydrogenate unsaturated acyl chains in the transformation of C20 polyunsaturated fatty acids (PUFAs) into the corresponding bioactive non-methylene-interrupted fatty acids (NMIFAs).

Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial.

BACKGROUND: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. PATIENTS AND METHODS: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. RESULTS: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). CONCLUSIONS: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.

Implementation of a Low-Field Portable MRI Scanner in a Resource-Constrained Environment: Our Experience in Malawi.

Low-field, portable MR imaging may expedite patient management in the setting of critical illness. We successfully implemented low-field MR imaging at the Queen Elizabeth Central Hospital in Malawi; a low-resource setting. We present our experience of low-field, portable MR imaging start-up and use in Malawi; the first of its kind in Sub-Saharan Africa, together with complementary troubleshooting mechanisms that may be used especially in similar resource-constrained contexts.

The Effect of Lipofilling and Platelet-Rich Plasma on Patients with Moderate-Severe Vulvar Lichen Sclerosus who were Non-Responders to Topical Clobetasol Propionate: A Randomized Pilot Study.

BACKGROUND: The first-line treatment for vulvar lichen sclerosus (VLS) is 3 months of topical corticosteroid therapy. However, limited evidence is available concerning the use of fat grafting and platelet-rich plasma as a second-line treatment for patients who do not respond to first-line treatment. METHODS: This prospective single-center randomized pilot trial included 20 patients with a clinical and histological diagnosis of moderate to severe VLS. The patients in the treatment group (TG) received two infiltrations (at 3-month intervals) of nanofat mixed with platelet-rich plasma (PRP) into the vulvar area, while the control group (CG) received standard topical corticosteroid therapy. Fat was aspirated from the medial thigh or lower abdomen regions. Microfat was obtained after centrifugation and was emulsified to obtain a nanofat suspension. Treatment efficacy was determined by measuring changes in the vulvar skin elasticity, histopathology, and clinical signs, symptoms, and patient quality of life at after 1 year. RESULTS: A total of 19 patients were finally assessed (9 TG and 10 CG). At the end of the study (1 year), there had been no significant improvement in vulvar skin elasticity. However, patients in the TG showed a significant improvement in their symptoms (itching, pain, burning, and dyspareunia) and clinical signs (cervical erosions, fissures, stenosis, and leukoderma). Analysis of skin biopsies revealed a significant decrease in all inflammatory cell types in the TG. No adverse events related to the autologous treatment were recorded. CONCLUSIONS: Compared with topical corticosteroids, two infiltrations delivered 3 months apart decreased the inflammation of the vulva and improved most of the clinical signs and symptoms associated with VLS. Nonetheless, no improvement in vulvar skin elasticity was derived from the autologous treatment. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Standardization of a high-performance RT-qPCR for viral load absolute quantification of influenza A.

Influenza is an acute viral infectious respiratory disease worldwide, presenting in different clinical forms, from influenza-like illness (ILI) to severe acute respiratory infection (SARI). Although real-time quantitative polymerase chain reaction (qPCR) is already an important tool for both diagnosis and treatment monitoring of several viral infections, the correlation between the clinical aspects and the viral load of influenza is still unclear. This lack of clarity is primarily due to the low accuracy and reproducibility of the methodologies developed to quantify the influenza virus. Thus, this study aimed to develop and standardize a universal absolute quantification for influenza A by reverse transcription-quantitative PCR (RT-qPCR), using a plasmid DNA. The assay showed efficiency (Eff%) 98.6, determination coefficient (R2) 0.998, linear range 10^1 to 10^10, limit of detection (LOD) 6.77, limit of quantification (LOQ) 20.52 copies/reaction. No inter and intra assay variability was shown, and neither was the matrix effect observed. Serial measurements of clinical samples collected at a 72h interval showed no change in viral load. By contrast, immunocompetent patients have a significantly lower viral load than immunosuppressed ones. Absolute quantification in clinical samples showed some predictors associated with increased viral load: (H1N1)pdm09 (0.045); women (p = 0.049) and asthmatics (p = 0.035). The high efficiency, precision, and previous performance in clinical samples suggest the assay can be used as an accurate universal viral load quantification of influenza A. Its applicability in predicting severity and response to antivirals needs to be evaluated.

Estudio de la identidad enfermera a partir del análisis iconográfico de la vestimenta de los profesionales a lo largo de la historia / Study of the nurse identity from the iconographic analysis of the clothing of professionals throughout history

Históricamente, se ha intentado definir el concepto de identidad profesional desde la relación que el propio profesio-nal establece con la sociedad, y como “un conjunto de atribu-tos que permiten al individuo sentirse parte de un gremio profesional”. Se trata de una variable contextual influenciados por coyunturas históricas y cultura-les, e incluso influenciado por discursos públicos (AU)

La historia de la Enfermería: retos pedagógicos actuales / Situation of Teaching Innovation of Nursing History in Spain: a descriptive study

Los últimos años, a pesar de que se ha producido un crecimiento en competencias y una mejora sustancial de la profesión enfermera como disciplina Académica, sigue siendo un colectivo con gran invisibilidad social en el que ganan terreno las actividades de carácter técnico frente a los saberes humanísticos que fundamentan mayoritariamente el rol autónomo en los cuidados [Fragmento de texto] (AU)